scholarly journals Tu1499 – Vitamin D Deficiency and Sustained Virologic Response on Antiviral Therapy with Pegylated Interferon Alpha 2 and Ribavirin in Patients with Chronic Hepatitis C, Genotype-1

2019 ◽  
Vol 156 (6) ◽  
pp. S-1344
Author(s):  
Elena Kukhareva ◽  
Olga Tarasova ◽  
Pavel Ogurtsov
2017 ◽  
Vol 95 (5) ◽  
pp. 438-444
Author(s):  
E. I. Kukhareva ◽  
P. P. Ogurtsov

Aim. To study effects of correction of vitamin D deficiency on the outcome of antiviral therapy (AVT) with PEGylated interferon alpha 2 (peg-IFN-α-2) and Ribavirin (RBV) in patients with genotype -1 chronic hepatitis C (CHC-1). Materials and methods. The study included 90 patients with primary HCV-1 and deficiency of vitamin D. In all patients of them, insulin resistance (HOMA-IR), body mass index (BMI), viral load, vitamin D levels, stage of liver fibrosis and polymorphism of the IL-28B gene were evaluated. Antiviral therapy included PEG-IFN-α-2 and RBV in combination with water-soluble vitamin D at a dose of 2000 mg/day. 55 patients were assigned to HCV-1 (study group). 35 patients with CHC-1 (control group) were given only PEG-IFN-α-2 + RBV. Results. Vitamin D level was inversely correlated with HOMA-IR, BMI (R = -0,5; R = -0,5; R = -0,4; respectively, p <0.05, Spearman) and inverse relationship between the level of vitamin D (25-Oh), BMI and HOMA-IR (β for BMI=-0,433 (95% CI -1,863;-0,697, p<0.001), HOMA-IR=-0,252 (95% Cl -1,873;-0,229, p=0,013) was documented based on the multiple regression analysis. In the study group, sustained virological response (SVR) was achieved in 74.5% of the patient compared with 42.9% in the control group; OR SVR in patients of the study group was 6.8 (95% Cl 2,90-16.09, p=0.002). SVR was reached in 66.7% and 22.2% patients of the study group with BMI>25 kg/m2 and controls respectively. OR SVR in patients with BMI over 25 kg/m2 who received cholecalciferol at AVT was 7.0 (95% Cl 1.66-29,23, p=0.01, Fisher test). In the patients with HOMA-IR>2.0, the frequency of SVR in the study qnd control groups was 66.7% and 37.5% respectively; OR SVR in patients with HOMA-IR>2.0 receiving colecalciferol at AVT was 3.3 (95% Cl 1.1-9.9, p=0.03, Fisher's exact test). In the study group a statistically significant decrease of HOMA-IR (p<0.001, Wilcoxon test) and undesirable effects of antiviral therapy (р<0,05) was documented. Conclusions. The addition of colecalciferol at a daily dose of 2000 IU to PEG-IFN-alpha-2+RBV therapy is safe and significantly increases the efficiency of AVT from 40.0 up to 74.5% (p=0.002), improves OR SVR up to 7.0 (95% Cl 1.66-29,23, p=0.01) in patients with BMI >25 kg/m2 and up to 3.3 (95% Cl 1.1-9.9, p=0.03) in patients with HOMA-IR>2; it significantly reduces HOMA-IR (p<0,0001) and the frequency of adverse effects (p<0.05).


2013 ◽  
Vol 58 (3) ◽  
pp. 467-472 ◽  
Author(s):  
Matthew T. Kitson ◽  
Gregory J. Dore ◽  
Jacob George ◽  
Peter Button ◽  
Geoffrey W. McCaughan ◽  
...  

2015 ◽  
Vol 59 (10) ◽  
pp. 6017-6025 ◽  
Author(s):  
K. L. Berger ◽  
J. Scherer ◽  
M. Ranga ◽  
N. Sha ◽  
J. O. Stern ◽  
...  

ABSTRACTAnalysis of data pooled from multiple phase 2 (SILEN-C1 to 3) and phase 3 studies (STARTVerso1 to 4) of the hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) protease inhibitor faldaprevir plus pegylated interferon alpha/ribavirin (PR) provides a comprehensive evaluation of baseline and treatment-emergent NS3/4A amino acid variants among HCV genotype-1 (GT-1)-infected patients. Pooled analyses of GT-1a and GT-1b NS3 population-based pretreatment sequences (n= 3,124) showed that faldaprevir resistance-associated variants (RAVs) at NS3 R155 and D168 were rare (<1%). No single, noncanonical NS3 protease or NS4A cofactor baseline polymorphism was associated with a reduced sustained virologic response (SVR) to faldaprevir plus PR, including Q80K. The GT-1b NS3 helicase polymorphism T344I was associated with reduced SVR to faldaprevir plus PR (P< 0.0001) but was not faldaprevir specific, as reduced SVR was also observed with placebo plus PR. Among patients who did not achieve SVR and had available NS3 population sequences (n= 507 GT-1a;n= 349 GT-1b), 94% of GT-1a and 83% of GT-1b encoded faldaprevir treatment-emergent RAVs. The predominant GT-1a RAV was R155K (88%), whereas GT-1b encoded D168 substitutions (78%) in which D168V was predominant (67%). The novel GT-1b NS3 S61L substitution emerged in 7% of virologic failures as a covariant with D168V, most often among the faldaprevir breakthroughs; S61L in combination with D168V had a minimal impact on faldaprevir susceptibility compared with that for D168V alone (1.5-fold differencein vitro). The median time to loss of D168 RAVs among GT-1b-infected patients who did not have a sustained virologic response at 12 weeks posttreatment (non-SVR12) after virologic failure was 5 months, which was shorter than the 14 months for R155 RAVs among GT-1a-infected non-SVR12 patients, suggesting that D168V is less fit than R155K in the absence of faldaprevir selective pressure.


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